Fernández-Galaz C, Fernández-Agulló T, Pérez C, Peralta S, Arribas C, Andrés A, Carrascosa J M, Ros M
Faculty of Health Sciences, University Rey Juan Carlos, Alcorcón, Madrid, Spain.
Diabetologia. 2002 Jul;45(7):997-1003. doi: 10.1007/s00125-002-0851-4. Epub 2002 Jun 19.
AIMS/HYPOTHESIS: Ageing is associated with insulin and leptin resistance in mammals. These alterations might be caused by the increased adiposity associated with ageing, by ageing alone or both. We studied whether leptin resistance occurs at the central level in the Wistar rat and we aimed to discriminate between the effects of ageing from those of the increased adiposity associated with ageing.
Leptin was infused intracerebroventricularly at a constant rate in young adult, old and old Wistar rats fasted for 3 months, using osmotic pumps. The effects on body weight, daily food intake, Lee index, adiposity and serum leptin values were analysed. The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied.
Leptin decreased daily food intake and body weight in young and old Wistar rats. With a dose of 10 microg/day similar responses were obtained in young and old rats but with a dose of 0.2 microg/day, only young rats showed decreases in these parameters. Food-restriction in old rats lowered adiposity and serum leptin to values close to those of young rats, recovered responsiveness to i.c.v. administration of leptin at the dose of 0.2 microg/day and increased leptin receptor expression in the hypothalamus.
CONCLUSION/INTERPRETATION: Our data show that old Wistar rats have a decreased response to leptin at the central level. Food-restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing.
目的/假设：衰老与哺乳动物的胰岛素和瘦素抵抗相关。这些改变可能是由与衰老相关的肥胖增加、衰老本身或两者共同引起的。我们研究了Wistar大鼠中枢水平是否存在瘦素抵抗，并旨在区分衰老的影响与与衰老相关的肥胖增加的影响。
使用渗透泵以恒定速率向禁食3个月的年轻成年、老年和老年Wistar大鼠脑室内注入瘦素。分析其对体重、每日食物摄入量、李氏指数、肥胖程度和血清瘦素值的影响。还研究了食物限制对下丘脑瘦素受体长型表达的影响。
瘦素降低了年轻和老年Wistar大鼠的每日食物摄入量和体重。剂量为10微克/天时，年轻和老年大鼠获得了相似的反应，但剂量为0.2微克/天时，只有年轻大鼠的这些参数出现下降。老年大鼠的食物限制降低了肥胖程度和血清瘦素水平，使其接近年轻大鼠的值，恢复了对0.2微克/天剂量的脑室内注射瘦素的反应性，并增加了下丘脑瘦素受体的表达。
结论/解读：我们的数据表明，老年Wistar大鼠在中枢水平对瘦素的反应降低。食物限制恢复了瘦素反应性并增加了下丘脑瘦素受体，表明肥胖在与衰老相关的瘦素抵抗发展中起关键作用。
